This program is aimed at better understanding how papovaviruses transform cells and induce tumors in animals. It focuses on major aspects of the transformation process from its earliest event, virus entry into a suitable target cell, to the full expression of a transformed phenotype. The fundamental theme of the work is that papovaviral transforming proteins function by perturbation of defined molecular events in intracellular signal transduction used in normal cell growth and differentiation. The aim of the program is to understand the nature of these viral-cellular protein interactions in detail and to learn how they contribute to the various elements in a neoplastic phenotype. Experiments with polyoma, SV40, and human papilloma virus transforming proteins are planned. In each case, detailed analyses of the actions of known cellular protein targets of these proteins will be undertaken. Special emphasis will be placed on attempting to learn how each of these signalling proteins functions normally and after contacting the relevant viral transforming protein. Since papovaviral oncoproteins interact with important signalling molecules active in both the proximal and distal ends of key growth regulating pathways, information gained in the program is also likely to enhance one's understanding of normal signalling.